Hyaluronic Acid is a naturally occurring high molecular weight polysaccharide having an empirical formula of C14H20NNa11 where n>1000. It is accepted that Hyaluronic Acid (HA) comes from three principle sources, human umbilical cords, rooster combs, and certain bacterial cultures from group A and C hemolytic streptococci. Commercial sources for HA are generally from umbilical cords and rooster combs. The present invention is derived from rooster combs.
HA was first isolated by Karl Meyer in 1934. He derived the novel glycosoaminoglycan from the vitreous of bovine eyes. The substance contained a uronic acid and an amino sugar, but no sulfoesters. Meyer's discovery is frequently referred to as Hylauron in vivo and Hyaluronic Acid (HA) ex vivo. The precise chemical structure was determined 20 years later and classified as part of biologically active molecules known as glycosoaminoglycans (GAGs). GAGs are principally located in or on the cellular membrane or in the material between cells called the extracellular matrix (ECM).
GAGs are long, unbranched polysaccharides containing a repeating disaccharide unit. In the case of Hyaluronan this disaccharide consists of D-glucuronate and D-acetylglucosamine. GAGs are negatively charged, high molecular weight molecules that have several unique properties. Among them is high viscosity in solution. High viscosity yields low compressibility resulting in excellent lubrication and shock absorption, particularly for soft tissues and joints. HA polymers are comparatively very large (i.e., having high molecular weight in the range of 1 million to 4 million daltons in a highly polymerized preparation) and can displace a large volume of water making them the body's premier lubricators.
HA is found in many tissues of the body. It is present in particularly high concentrations in the synovial fluid that lubricates the joints, in heart valve tissue, in the fluids of the inner ear, in many layers of the skin, especially the dermis, and in the vitreous humor of the eyes.
The preparation HA from rooster combs and human umbilical cords for use in eye and joint applications is described in U.S. Pat. No. 4,141,973 to E. A. Balazs. This patent provides a detailed review of the technical literature describing the isolation, characterization and uses of HA. U.S. Pat. No. 4,303,676 also to E. A. Balazs describes the cosmetic formulations containing Hyaluronate fractions in various molecular weight ranges made from rooster combs. U.S. Pat. No. 4,328,803 to L. G. Pape describes the use of an ultra-pure Hyaluronic Acid salt utilized in eye surgery. The HA product used here was a sodium Hyaluronate salt available under the registered trademark HYARTIL.RTM from Pharmacia, Inc. and obtained in commercial quantities from rooster combs as well.
The purpose it has in each of these applications is slightly different, but all are based on the principles of cellular hydration and separation. The hydration provided by HA allows for the proper transfer of nutrition and elimination of waste. In a sense, cells are bathed in a framework of HA. This framework allows the exchange of not just nutrition, but also regulatory and communication chemicals through the space between cells. Until recently, it was thought that HA was largely inert, that it simply filled the space between cells. This space, called the extra cellular matrix (ECM) is filled with a ground substance. The ground substance is primarily HA.
As Meyer observed when discussing sulfoesters, HA is unique among the GAGs because it does not contain sulfate and is not bonded to proteins as a proteoglycan. It is, however, a component of proteoglycans in the ECM. This gives HA great flexibility in providing scalable structural integrity through visco-elastic support necessary for separation between tissues while facilitating immune functions or intercellular communication. HA in the ECM helps control tissue permeation, bacterial invasiveness, and macromolecular transport between cells. HA also plays an important role in mediating how cells of neighboring tissues interact and communicate.
The body's need for HA is great. Not only is it an important part of tissue structure, but it also provides active support and binding sites for intracellular interactions, acts as a buffer zone to protect cells, and forms part of the waste complexes that is frequently eliminated from tissues frequently. Because of this, HA is catabolized in many tissues and must be renewed constantly.
Certain cells such as chondrocytes in the cartilage and keratinocytes in the epidermis actively synthesize and catabolize HA throughout a person's life span. Hascall et al. has found that the half-life of an HA molecule to be normally 2-3 weeks, while the half-life in the epidermis is amazingly less than one day. This production decreases with a person's increased age. Any means of increasing the amount of HA in the body promises to have great benefits in improving the quality, elasticity, and function of the skin and joints. Till now, large/high molecular weight HA has been topically applied in cosmetic products and injected in medical preparations for joint health.
Other attempts take the form of supplementing with HA components, namely chondroitin and glucosamine. While these are both effective in helping to augment the functions of HA in the joints, they have not been proven to assist in the intercellular functions of HA nor do they affect HA levels directly as far as it is known.